Search

The presence of ATP is known to stimulate helicase activity of the Dengue Virus Non-structural protein 3 helicase (NS3h), and the presence of RNA stimulates NS3h ATPase activity, however this coupling is still mechanistically unclear. Here we use atomistic models and molecular dynamics simulations to evaluate the single-stranded RNA (ssRNA)-length dependence of the NS3h-ssRNA binding affinity and its modulation by bound ATP. Considering complexes with 7, 11, 16 and 26 nucleotides (nts), we observe that both the binding affinity and its modulation by bound ATP are augmented with increased ssRNA lengths. In models with at least 11 nts bound, the binding of ATP results in a shift from a tightly bound to a weakly bound state. We find that the weakly bound state persists during both the ADP-Pi- and ADP-bound stages of the catalytic cycle. We obtain the equilibrium association constants for NS3h binding to an ssRNA 10-mer in vitro, both in the absence and presence of ADP, which further support the alternation between tightly and weakly bound states during the catalytic cycle. The length of bound ssRNA is critical for understanding the NS3h-RNA interaction as well as how it is modulated during the catalytic cycle., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

The Dengue Virus (DENV) non-structural protein 3 (NS3) is a multi-functional protein critical in the viral life cycle. The DENV NS3 is comprised of a serine protease domain and a helicase domain. The helicase domain itself acts as a molecular motor, either translocating in a unidirectional manner along single-stranded RNA or unwinding double-stranded RNA, processes fueled by the hydrolysis of nucleoside triphosphates. In this brief review, we summarize our contributions and ongoing efforts to uncover the thermodynamic and mechanistic functional properties of the DENV NS3 as an NTPase and helicase., Competing Interests: Conflict of interestThe authors declare no competing interests., (© International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag GmbH Germany, part of Springer Nature 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Fijiviruses replicate and package their genomes within viroplasms in a process involving RNA-RNA and RNA-protein interactions. Here, we demonstrate that the 24 C-terminal residues (C-arm) of the P9-1 major viroplasm protein of the mal de Río Cuarto virus (MRCV) are required for its multimerization and the formation of viroplasm-like structures. Using an integrative structural approach, the C-arm was found to be dispensable for P9-1 dimer assembly but essential for the formation of pentamers and hexamers of dimers (decamers and dodecamers), which favored RNA binding. Although both P9-1 and P9-1ΔC-arm catalyzed ATP with similar activities, an RNA-stimulated ATPase activity was only detected in the full-length protein, indicating a C-arm-mediated interaction between the ATP catalytic site and the allosteric RNA binding sites in the (do)decameric assemblies. A stronger preference to bind phosphate moieties in the decamer was predicted, suggesting that the allosteric modulation of ATPase activity by RNA is favored in this structural conformation. Our work reveals the structural versatility of a fijivirus major viroplasm protein and provides clues to its mechanism of action. IMPORTANCE The mal de Río Cuarto virus (MRCV) causes an important maize disease in Argentina. MRCV replicates in several species of Gramineae plants and planthopper vectors. The viral factories, also called viroplasms, have been studied in detail in animal reovirids. This work reveals that a major viroplasm protein of MRCV forms previously unidentified structural arrangements and provides evidence that it may simultaneously adopt two distinct quaternary assemblies. Furthermore, our work uncovers an allosteric communication between the ATP and RNA binding sites that is favored in the multimeric arrangements. Our results contribute to the understanding of plant reovirids viroplasm structure and function and pave the way for the design of antiviral strategies for disease control.

Methanogenic archaea have received attention due to their potential use in biotechnological applications such as methane production, so their metabolism and regulation are topics of special interest. When growing in a nutrient-rich medium, these organisms exhibit gluconeogenic metabolism; however, under starvation conditions, they turn to glycolytic metabolism. To date, no regulatory mechanism has been described for this gluconeogenic/glycolytic metabolic switch. Here, we report that adenosine monophosphate (AMP) activates both enzymatic activities of the bifunctional adenosine diphosphate (ADP)-dependent phosphofructokinase/glucokinase from Methanococcus maripaludis (MmPFK/GK). To understand this phenomenon, we performed a comprehensive kinetic characterisation, including determination of the kinetics, substrate inhibition and AMP activation mechanism of this enzyme. We determined that MmPFK/GK has an ordered-sequential mechanism, in which MgADP is the first substrate to bind and AMP is the last product released. The enzyme also displays substrate inhibition by both sugar substrates; we determined that this inhibition occurs through the formation of catalytically nonproductive enzyme complexes caused by sugar binding. For both activities, the AMP activation mechanism occurs primarily through incremental changes in the affinity for the sugar substrate, with this effect being higher in the GK than in the PFK activity. Interestingly, due to the increase in the sugar substrate affinity caused by AMP, an enhancement in the sugar substrate inhibition effect was also observed for both activities, which can be explained by an increase in sugar binding leading to the formation of dead-end complexes. These results shed light on the regulatory mechanisms of methanogenic archaeal sugar metabolism, a phenomenon that has been largely unexplored., (© 2022 Federation of European Biochemical Societies.)

Objective: Narcissism can manifest in grandiose and vulnerable patterns of experience and behavior. While largely unrelated in the general population, individuals with clinically relevant narcissism are thought to display both. Our previous studies showed that trait measures of grandiosity and vulnerability were unrelated at low-to-moderate levels of grandiose narcissism, but related at high levels., Method: We replicate and extend these findings in a preregistered individual data meta-analysis ("mega-analysis") using data from the Narcissistic Personality Inventory (NPI)/Hypersensitive Narcissism Scale (HSNS; N = 10,519, k = 28) and the Five-Factor Narcissism Inventory (FFNI; N = 7,738, k = 17)., Results: There was strong evidence for the hypothesis in the FFNI (β Grandiose < 1 SD  = .08, β Grandiose > 1 SD  = .36, β Grandiose > 2 SD  = .53), and weaker evidence in the NPI/HSNS (β Grandiose < 1 SD  = .00, β Grandiose > 1 SD  = .12, β Grandiose > 2 SD  = .32). Nonlinearity increased with age but was invariant across other moderators. Higher vulnerability was predicted by elevated antagonistic and low agentic narcissism at subfactor level., Conclusion: Narcissistic vulnerability increases at high levels of grandiosity. Interpreted along Whole Trait Theory, the effects are thought to reflect state changes echoing in trait measures and can help to link personality and clinical models., (© 2021 The Authors. Journal of Personality published by Wiley Periodicals LLC.)

How should I greet her? Should I do what he requests? Newcomers to a culture learn its interpersonal norms at varying rates, largely through trial-and-error experience. Given that the culturally correct response often depends on conditions that are subtle and complex, we propose that newcomers' rate of acculturation depends on not only their explicit aptitude (e.g., reasoning ability) but also their implicit aptitude (e.g., pattern recognition ability). In Studies 1-3, participants experienced a range of influence situations sourced from a foreign culture. Across many trials, they decided whether or not to comply and then received accuracy feedback (based on what a majority of locals indicated to be the appropriate action in each situation). Across the 3 studies, stronger implicit aptitude was associated with greater improvement from trial-and-error experience, whereas stronger explicit aptitude was not. In Studies 4-6, participants experienced a range of greeting situations from a foreign culture. Across many trials, implicit aptitude predicted experiential learning, especially under conditions that impede reasoning: multiple cues, subliminal feedback, or inconsistent feedback. Study 7 found that the predictiveness of implicit aptitude was weaker under a condition that impedes associative processing: delayed feedback. These findings highlight the important role of implicit aptitude in helping people learn interpersonal norms from trial-and-error experience, particularly because in real-life intercultural interactions, the relevant cues are often complex, and the feedback is often fleeting and inconsistent but immediate. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The non-structural protein 3 helicase (NS3h) is a multifunctional protein that is critical in RNA replication and other stages in the flavivirus life cycle. NS3h uses energy from ATP hydrolysis to translocate along single stranded nucleic acid and to unwind double stranded RNA. Here we present a detailed mechanistic analysis of the product release stage in the catalytic cycle of the dengue virus (DENV) NS3h. This study is based on a combined experimental and computational approach of product-inhibition studies and free energy calculations. Our results support a model in which the catalytic cycle of ATP hydrolysis proceeds through an ordered sequential mechanism that includes a ternary complex intermediate (NS3h-Pi-ADP), which evolves releasing the first product, phosphate (Pi), and subsequently ADP. Our results indicate that in the product release stage of the DENV NS3h a novel open-loop conformation plays an important role that may be conserved in NS3 proteins of other flaviviruses as well., (© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)

DBS Think Tank IX was held on August 25-27, 2021 in Orlando FL with US based participants largely in person and overseas participants joining by video conferencing technology. The DBS Think Tank was founded in 2012 and provides an open platform where clinicians, engineers and researchers (from industry and academia) can freely discuss current and emerging deep brain stimulation (DBS) technologies as well as the logistical and ethical issues facing the field. The consensus among the DBS Think Tank IX speakers was that DBS expanded in its scope and has been applied to multiple brain disorders in an effort to modulate neural circuitry. After collectively sharing our experiences, it was estimated that globally more than 230,000 DBS devices have been implanted for neurological and neuropsychiatric disorders. As such, this year's meeting was focused on advances in the following areas: neuromodulation in Europe, Asia and Australia; cutting-edge technologies, neuroethics, interventional psychiatry, adaptive DBS, neuromodulation for pain, network neuromodulation for epilepsy and neuromodulation for traumatic brain injury., Competing Interests: RR was employed by Medtronic, Inc. HBo was employed by Boston Scientific Neuromodulation Corporation. DG was employed by the NeuroPace, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wong, Deuschl, Wolke, Bergman, Muthuraman, Groppa, Sheth, Bronte-Stewart, Wilkins, Petrucci, Lambert, Kehnemouyi, Starr, Little, Anso, Gilron, Poree, Kalamangalam, Worrell, Miller, Schiff, Butson, Henderson, Judy, Ramirez-Zamora, Foote, Silburn, Li, Oyama, Kamo, Sekimoto, Hattori, Giordano, DiEuliis, Shook, Doughtery, Widge, Mayberg, Cha, Choi, Heisig, Obatusin, Opri, Kaufman, Shirvalkar, Rozell, Alagapan, Raike, Bokil, Green and Okun.)

Memorializes Jerome L. Singer (1924-2019). Singer's seminal research, conducted over 50þ years, laid the foundations for virtually all modern investigations of stream of consciousness and mind wandering. During a time when daydreaming was considered pathological, Singer showed it to be a pervasive aspect of human experience that served positive social and creative functions, earning him the moniker "the father of daydreaming." After receiving his PhD in clinical psychology in 1951, Singer was certified as a psychoanalyst through the William Alanson White Institute, while also holding several part-time research appointments. In 1963, Singer became director of the clinical psychology program at City University, where he and collaborator John Antrobus studied "decoupled attention." Singer joined the faculty of Yale University in 1972 and assumed emeritus status in 2006. At Yale, he worked closely with his wife Dorothy (who was an exemplary developmental psychologist in her own right), where they codirected Yale's Family TV Research and Consultation Center for more than 30 years. He died on December 14, 2019. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

An influential model of the neural mechanisms of creative thought suggests that creativity is manifested in the joint contributions of the Default Mode Network (DMN; a set of regions in the medial PFC, lateral and medial parietal cortex, and the medial temporal lobes) and the executive networks within the dorsolateral PFC. Several empirical reports have offered support for this model by showing that complex interactions between these brain systems account for individual differences in creative performance. The present study examined whether the engagement of these regions in idea generation is modulated by one's eminence in a creativity-related field. Twenty (n ​= ​20) healthy eminent creators from diverse fields of expertise and a 'smart' comparison group of sixteen (n ​= ​16) age- and education-matched non-eminent thinkers were administered a creative generation task (an adaptation of the Alternative Uses Task) and a control perceptual task, while undergoing functional magnetic resonance imaging (fMRI). The participants' verbal responses were recorded through a noise-canceling microphone and were later coded for fluency and accuracy. Behavioral and fMRI analyses revealed commonalities between groups, but also distinct patterns of activation in default mode and executive brain regions between the eminent and the non-eminent participants during creative thinking. We interpret these findings in the context of the well-documented contributions of these regions in the generation of creative ideas as modulated, in this study, by participants' creative eminence., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Nearly everyone has the ability for creative thought. Yet, certain individuals create works that propel their fields, challenge paradigms, and advance the world. What are the neurobiological factors that might underlie such prominent creative achievement? In this study, we focus on morphometric differences in brain structure between high creative achievers from diverse fields of expertise and a 'smart' comparison group of age-, intelligence-, and education-matched average creative achievers. Participants underwent a high-resolution structural brain imaging scan and completed a series of intelligence, creative thinking, personality, and creative achievement measures. We examined whether high and average creative achievers could be distinguished based on the relationship between morphometric brain measures (cortical area and thickness) and behavioral measures. Although participants' performance on the behavioral measures did not differ between the two groups aside from creative achievement, the relationship between posterior parietal cortex morphometry and creativity, intelligence, and personality measures depended on group membership. These results suggest that extraordinary creativity may be associated with measurable structural brain differences, especially within parietal cortex., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Dengue represents a substantial public health burden, particularly in low-resource countries. Non-structural protein 3 (NS3) is a multifunctional protein critical in the virus life cycle and has been identified as a promising anti-viral drug target. Despite recent crystallographic studies of the NS3 helicase domain, only subtle structural nucleotide-dependent differences have been identified, such that its coupled ATPase and helicase activities remain mechanistically unclear. Here we use molecular dynamics simulations to explore the nucleotide-dependent conformational landscape of the Dengue virus NS3 helicase and identify substantial changes in the protein flexibility during the ATP hydrolysis cycle. We relate these changes to the RNA-protein interactions and proposed translocation models for other monomeric helicases. Furthermore, we report a novel open-loop conformation with a likely escape route for P i after hydrolysis, providing new insight into the conformational changes that underlie the ATPase activity of NS3., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Selfishness is often regarded as an undesirable or even immoral characteristic, whereas altruism is typically considered universally desirable and virtuous. However, human history as well as the works of humanistic and psychodynamic psychologists point to a more complex picture: not all selfishness is necessarily bad, and not all altruism is necessarily good. Based on these writings, we introduce new scales for the assessment of individual differences in two paradoxical forms of selfishness that have lacked measurement in the field - healthy selfishness (HS) and pathological altruism (PA). In two studies ( N 1 = 370, N 2 = 891), we constructed and validated the HS and PA scales. The scales showed good internal consistency and a clear two-dimensional structure across both studies. HS was related to higher levels of psychological well-being and adaptive psychological functioning as well as a genuine prosocial orientation. PA was associated with maladaptive psychological outcomes, vulnerable narcissism, and selfish motivations for helping others. These results underpin the paradoxical nature of both constructs. We discuss the implications for future research, including clinical implications., (Copyright © 2020 Kaufman and Jauk.)

There is broad consensus that there are at least two different dimensions of narcissism: vulnerable and grandiose. In this study, the authors use a new trifurcated, three-factor model of narcissism to examine relations between aspects of narcissism and an array of clinically relevant criteria related to psychopathology, the self, authenticity, and well-being. Neurotic and antagonistic aspects of narcissism emerged as the most clinically relevant dimensions of narcissism, bearing relations with outcomes relating to interpersonal guilt, insecure attachment styles, cognitive distortions, maladaptive defense mechanisms, experiential avoidance, impostor syndrome, weak sense of self, inauthenticity, low self-esteem, and reduced psychological well-being. Grandiose narcissism was not correlated with most forms of psychopathology and was even positively associated with life satisfaction. Nevertheless, a surprising link was found between grandiose narcissism and multiple indicators of inauthenticity. Implications for the appropriate conceptualization, assessment, and treatment of pathological narcissism are discussed.

Dengue virus nonstructural protein 3 (NS3) fulfills multiple essential functions during the viral replication and constitutes a prominent drug target. NS3 is composed by a superfamily-2 RNA helicase domain joined to a serine protease domain. Quantitative fluorescence titrations employing a fluorescein-tagged RNA oligonucleotide were used to investigate the effect of salts on the interaction between NS3 and single stranded RNA (ssRNA). We found a strong dependence of the observed equilibrium binding constant, K obs , with the salt concentration, decreasing at least 7-fold for a 1-fold increase on cation concentration. As a result of the effective neutralization of ~10 phosphate groups, binding of helicase domain of NS3 to ssRNA is accompanied by the release of 5 or 7 monovalent cations from an oligonucleotide or a polynucleotide, respectively and of 3 divalent cations from the same oligonucleotide. Such estimates are not affected by the type of cation, either monovalent (KCl, NaCl and RbCl) or divalent (MgCl 2 and CaCl 2 ), nor by the presence of the protease domain or the fluorescein label. Combined effect of mono and divalent cations was well described by a simple equilibrium binding model which allows to predict the values of K obs at any concentration of cations.

While there is a growing literature on "dark traits" (i.e., socially aversive traits), there has been a lack of integration with the burgeoning research literature on positive traits and fulfilling and growth-oriented outcomes in life. To help move the field toward greater integration, we contrasted the nomological network of the Dark Triad (a well-studied cluster of socially aversive traits) with the nomological network of the Light Triad, measured by the 12-item Light Triad Scale (LTS). The LTS is a first draft measure of a loving and beneficent orientation toward others ("everyday saints") that consists of three facets: Kantianism (treating people as ends unto themselves), Humanism (valuing the dignity and worth of each individual), and Faith in Humanity (believing in the fundamental goodness of humans). Across four demographically diverse samples ( N = 1,518), the LTS demonstrated excellent reliability and validity, predicting life satisfaction and a wide range of growth-oriented and self-transcendent outcomes above and beyond existing measures of personality. In contrast, the Dark Triad was negatively associated with life satisfaction and growth-oriented outcomes, and showed stronger linkages to selfish, exploitative, aggressive, and socially aversive outcomes. This exploratory study of the contrasting nomological networks of the Light vs. Dark Triad provides several ways forward for more principled and data driven approaches to explore both the malevolent and beneficent sides of human nature.

Narcissism is a truly Janusian phenomenon, consisting of both narcissistic grandiosity, exhibitionism, admiration-seeking, boldness, and dominance on the one hand, and narcissistic vulnerability, introversion, withdrawal, hypersensitivity, and anxiety on the other hand. While there is broad consensus that these two seemingly contradictory faces of narcissism can be empirically discerned and have different implications for psychological functioning and mental health, there is not yet agreement on whether grandiose and vulnerable narcissism should be regarded as independent traits or as two manifestations of one personality trait. Previous research indicates that both views hold true when the level of grandiosity is considered a moderating factor: while grandiose and vulnerable narcissism are largely unrelated in the range of normal personality variation, they are correlated in the range of high grandiosity (Jauk et al., 2017b). Here, we replicate and extend this work in an independent sample ( N = 891) using a more comprehensive narcissism inventory grounded in a new trifurcated model of narcissism. The trifurcated model partitions narcissism into three main personality dimensions: agentic extraversion, antagonism, and neuroticism. We found a significant breakpoint in the association between narcissistic grandiosity and vulnerability at 75% cumulative frequency of grandiosity. While grandiosity and vulnerability are unrelated below this breakpoint ( r = 0.02), they are strongly correlated above ( r = 0.45). In the lower range of grandiose narcissism, grandiosity draws more upon agentic extraversion and is largely associated with mental health. In the upper range, however, grandiosity is more strongly linked to antagonism and is substantially associated with fear, negative affect, and depression. These findings provide evidence for the view that grandiose and vulnerable narcissism are distinct traits at lower levels of grandiosity, but blend into an antagonistic core with signs of psychological maladjustment at higher levels. Implications for research on narcissism as a personality trait, as well as clinical practice, are discussed.

Objective: Personality traits are associated with well-being, but the precise correlates vary across well-being dimensions and within each Big Five domain. This study is the first to examine the unique associations between the Big Five aspects (rather than facets) and multiple well-being dimensions., Method: Two samples of U.S. participants (total N = 706; M age  = 36.17; 54% female) recruited via Amazon's Mechanical Turk completed measures of the Big Five aspects and subjective, psychological, and PERMA well-being., Results: One aspect within each domain was more strongly associated with well-being variables. Enthusiasm and Withdrawal were strongly associated with a broad range of well-being variables, but other aspects of personality also had idiosyncratic associations with distinct forms of positive functioning (e.g., Compassion with positive relationships, Industriousness with accomplishment, and Intellect with personal growth)., Conclusions: An aspect-level analysis provides an optimal (i.e., parsimonious yet sufficiently comprehensive) framework for describing the relation between personality traits and multiple ways of thriving in life., (© 2016 Wiley Periodicals, Inc.)

Na + ,K + -ATPase is an integral membrane protein which couples ATP hydrolysis to the transport of three Na + out and two K + into the cell. The aim of this work is to characterize the effect of K + , ATP, and Mg 2+ (essential activator) on the Na + ,K + -ATPase thermal stability. Under all conditions tested, thermal inactivation of the enzyme is concomitant with a structural change involving the ATP binding site and membrane-associated regions. Both ligands exert a clear stabilizing effect due to both enthalpic and entropic contributions. Competition experiments between ATP and K + showed that, when ATP is present, the inactivation rate coefficient exhibits a biphasic dependence on K + concentration. At low [K + ], destabilization of the enzyme is observed, while stabilization occurred at larger cation concentrations. This is not expected for a simple competition between the enzyme and two ligands that individually protect the enzyme. A model that includes enzyme species with none, one, or two K + and/or one molecule of ATP bound explains the experimental data. We concluded that, despite both ligands stabilizing the enzyme, the species with one K + and one ATP simultaneously bound is unstable.

The field of psychology has done a remarkable job discovering the ways people differ from one another in their abilities and talents, but has long neglected the diverse ways people can unleash those capacities. There is no plausible mechanism by which our genes directly encode skills like how to dribble a basketball, play the violin, or solve an algebraic equation. We are not born knowing how to write a sonnet or flip an omelet. On the contrary, all human expertise-even at the far-right tail of the distribution-depends on experience and training. A more accurate understanding of the development of high achievement should inspire people to push beyond their perceived and often self-imposed limits to reach heights they never would have imagined possible. WIREs Cogn Sci 2017, 8:e1365. doi: 10.1002/wcs.1365 For further resources related to this article, please visit the WIREs website., (© 2015 Wiley Periodicals, Inc.)

Evidence from education, psychology, and neuroscience suggests that investing in the development of the social-emotional imagination is essential to cultivating giftedness in adolescents. Nurturing these capacities may be especially effective for promoting giftedness in students who are likely to lose interest and ambition over time. Giftedness is frequently equated with high general intelligence as measured by IQ tests, but this narrow conceptualization does not adequately capture students' abilities to utilize their talents strategically to fully realize their future possible selves. The brain's default mode network is thought to play an important role in supporting imaginative thinking about the self and others across time. Because this network's functioning is temporarily attenuated when individuals engage in task- and action-oriented focus (mindsets thought to engage the brain's executive attention network), we suggest that consistently focusing students on tasks requiring immediate action could undermine long-term cultivation of giftedness. We argue that giftedness-especially in science, technology, engineering, and mathematics (STEM)-can be cultivated by encouraging adolescents' intellectual curiosity and supporting their ability to connect schoolwork to a larger purpose. Improving STEM and gifted education may depend upon a shift from knowledge transmission and regimented evaluation to creative exploration, intentional reflectiveness, and mindful switching between task focus and imagining., (© 2016 New York Academy of Sciences.)

The Big Five personality dimension Openness/Intellect is the trait most closely associated with creativity and creative achievement. Little is known, however, regarding the discriminant validity of its two aspects-Openness to Experience (reflecting cognitive engagement with perception, fantasy, aesthetics, and emotions) and Intellect (reflecting cognitive engagement with abstract and semantic information, primarily through reasoning)-in relation to creativity. In four demographically diverse samples totaling 1,035 participants, we investigated the independent predictive validity of Openness and Intellect by assessing the relations among cognitive ability, divergent thinking, personality, and creative achievement across the arts and sciences. We confirmed the hypothesis that whereas Openness predicts creative achievement in the arts, Intellect predicts creative achievement in the sciences. Inclusion of performance measures of general cognitive ability and divergent thinking indicated that the relation of Intellect to scientific creativity may be due at least in part to these abilities. Lastly, we found that Extraversion additionally predicted creative achievement in the arts, independently of Openness. Results are discussed in the context of dual-process theory., (© 2014 Wiley Periodicals, Inc.)

The brain's default network (DN) has been a topic of considerable empirical interest. In fMRI research, DN activity is associated with spontaneous and self-generated cognition, such as mind-wandering, episodic memory retrieval, future thinking, mental simulation, theory of mind reasoning, and creative cognition. Despite large literatures on developmental and disease-related influences on the DN, surprisingly little is known about the factors that impact normal variation in DN functioning. Using structural equation modeling and graph theoretical analysis of resting-state fMRI data, we provide evidence that Openness to Experience-a normally distributed personality trait reflecting a tendency to engage in imaginative, creative, and abstract cognitive processes-underlies efficiency of information processing within the DN. Across two studies, Openness predicted the global efficiency of a functional network comprised of DN nodes and corresponding edges. In Study 2, Openness remained a robust predictor-even after controlling for intelligence, age, gender, and other personality variables-explaining 18% of the variance in DN functioning. These findings point to a biological basis of Openness to Experience, and suggest that normally distributed personality traits affect the intrinsic architecture of large-scale brain systems. Hum Brain Mapp 37:773-779, 2016. © 2015 Wiley Periodicals, Inc., (© 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.)

Cooperative binding is one of the most interesting and not fully understood phenomena involved in control and regulation of biological processes. Here we analyze the simplest phenomenological model that can account for cooperativity (i.e. ligand binding to a macromolecule with two binding sites) by generating equilibrium binding isotherms from deterministically simulated binding time courses. We show that the Hill coefficients determined for cooperative binding, provide a good measure of the Gibbs free energy of interaction among binding sites, and that their values are independent of the free energy of association for empty sites. We also conclude that although negative cooperativity and different classes of binding sites cannot be distinguished at equilibrium, they can be kinetically differentiated. This feature highlights the usefulness of pre-equilibrium time-resolved strategies to explore binding models as a key complement of equilibrium experiments. Furthermore, our analysis shows that under conditions of strong negative cooperativity, the existence of some binding sites can be overlooked, and experiments at very high ligand concentrations can be a valuable tool to unmask such sites.

The role of attention in creative cognition remains controversial. Neuroimaging studies have reported activation of brain regions linked to both cognitive control and spontaneous imaginative processes, raising questions about how these regions interact to support creative thought. Using functional magnetic resonance imaging (fMRI), we explored this question by examining dynamic interactions between brain regions during a divergent thinking task. Multivariate pattern analysis revealed a distributed network associated with divergent thinking, including several core hubs of the default (posterior cingulate) and executive (dorsolateral prefrontal cortex) networks. The resting-state network affiliation of these regions was confirmed using data from an independent sample of participants. Graph theory analysis assessed global efficiency of the divergent thinking network, and network efficiency was found to increase as a function of individual differences in divergent thinking ability. Moreover, temporal connectivity analysis revealed increased coupling between default and salience network regions (bilateral insula) at the beginning of the task, followed by increased coupling between default and executive network regions at later stages. Such dynamic coupling suggests that divergent thinking involves cooperation between brain networks linked to cognitive control and spontaneous thought, which may reflect focused internal attention and the top-down control of spontaneous cognition during creative idea production.

Dengue virus nonstructural protein 3 (NS3) is a multifunctional protein formed by a superfamily-2 RNA helicase linked to a protease domain. In this work, we report results from in vitro experiments designed to determine the oligomeric state of dengue virus NS3 helicase (NS3h) and to characterize fundamental properties of the interaction with single-stranded (ss)RNA. Pulsed field gradient-NMR spectroscopy was used to determine the effective hydrodynamic radius of NS3h, which was constant over a wide range of protein concentrations in the absence and presence of ssRNA. Size exclusion chromatography-static light scattering experiments showed that NS3h eluted as a monomeric molecule even in the presence of ssRNA. Binding of NS3h to ssRNA was studied by quantitative fluorescence titrations using fluorescein-labeled and unlabeled ssRNA oligonucleotides of different lengths, and the effect of the fluorescein label on the interaction parameters was also analyzed. Experimental results were well described by a statistical thermodynamic model based on the theory of non-specific interactions of large ligands to a one-dimensional lattice. We found that binding of NS3h to ssRNA oligonucleotides and to poly(A) is characterized by minimum and occluded binding site sizes both of 10 nucleotides and by a weak positive cooperativity between adjacent proteins., (© The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Nearly 60 years ago, Jerome L. Singer launched a groundbreaking research program into daydreaming (Singer, 1955, 1975, 2009) that presaged and laid the foundation for virtually every major strand of mind wandering research active today (Antrobus, 1999; Klinger, 1999, 2009). Here we review Singer's enormous contribution to the field, which includes insights, methodologies, and tools still in use today, and trace his enduring legacy as revealed in the recent proliferation of mind wandering studies. We then turn to the central theme in Singer's work, the adaptive nature of positive constructive daydreaming, which was a revolutionary idea when Singer began his work in the 1950s and remains underreported today. Last, we propose a new approach to answering the enduring question: Why does mind wandering persist and occupy so much of our time, as much as 50% of our waking time according to some estimates, if it is as costly as most studies suggest?

Dengue virus nonstructural protein 3 (NS3) unwinds double stranded RNA driven by the free energy derived from the hydrolysis of nucleoside triphosphates. This paper presents the first systematic and quantitative characterization of the steady-state NTPase activity of DENV NS3 and their interaction with ssRNA. Substrate curves for ATP, GTP, CTP and UTP were obtained, and the specificity order for these nucleotides - evaluated as the ratio (kcat /KM )- was GTP[Formula: see text]ATP[Formula: see text]CTP [Formula: see text] UTP, which showed that NS3 have poor ability to discriminate between different NTPs. Competition experiments between the four substrates indicated that all of them are hydrolyzed in one and the same catalytic site of the enzyme. The effect of ssRNA on the ATPase activity of NS3 was studied using poly(A) and poly(C). Both RNA molecules produced a 10 fold increase in the turnover rate constant (kcat ) and a 100 fold decrease in the apparent affinity (KM ) for ATP. When the ratio [RNA bases]/[NS3] was between 0 and [Formula: see text]20 the ATPase activity was inhibited by increasing both poly(A) and poly(C). Using the theory of binding of large ligands (NS3) to a one-dimensional homogeneous lattice of infinite length (RNA) we tested the hypothesis that inhibition is the result of crowding of NS3 molecules along the RNA lattices. Finally, we discuss why this hypothesis is consistent with the idea that the ATPase catalytic cycle is tightly coupled to the movement of NS3 helicase along the RNA.

Folding and structural stability are key factors for the proper biological function of proteins. Na(+),K(+)-ATPase is an integral membrane protein involved in the active transport of Na(+) and K(+) across the plasma membrane. In this work we characterized the effects of K(+) and Na(+) on the thermal inactivation of Na(+),K(+)-ATPase, evaluating both catalytic and transport capacities of the pump. Both activities of the enzyme decrease with the preincubation time as first-order kinetics. The thermal inactivation of Na(+),K(+)-ATPase is simultaneous with a conformational change detected by tryptophan and 1-aniline-8-naphtalenesulfonate (ANS) fluorescence. The kinetic coefficient of thermal inactivation was affected by the presence of Na(+) and K(+) (or Rb(+)) and the temperature of the preincuabtion media. Our results show that K(+) or Rb(+) stabilize the enzyme, while Na(+) decreases the stability of Na(+),K(+)-ATPase. Both effects are exerted by the specific binding of these cations to the pump. Also, we provided strong evidence that the Rb(+) (or K(+)) stabilization effect is due to the occlusion of these cations into the enzyme. Here, we proposed a minimal kinetic model that explains the behavior observed in the experimental results and allows a better understanding of the results presented by other researchers. The thermal inactivation process was also analyzed according to Kramer's theory., (© 2012 American Chemical Society)

The flavivirus nonstructural protein 3 (NS3) bears multiple enzymatic activities and represents an attractive target for antiviral intervention. NS3 contains the viral serine protease at the N-terminus and ATPase, RTPase, and helicase activities at the C-terminus. These activities are essential for viral replication; however, the biological role of RNA remodeling by NS3 helicase during the viral life cycle is still unclear. Secondary and tertiary RNA structures present in the viral genome are crucial for viral replication. Here, we used the NS3 protein from dengue virus to investigate functions of NS3 associated to changes in RNA structures. Using different NS3 variants, we characterized a domain spanning residues 171 to 618 that displays ATPase and RNA unwinding activities similar to those observed for the full-length protein. Interestingly, we found that, besides the RNA unwinding activity, dengue virus NS3 greatly accelerates annealing of complementary RNA strands with viral or non-viral sequences. This new activity was found to be ATP-independent. It was determined that a mutated NS3 lacking ATPase activity retained full-RNA annealing activity. Using an ATP regeneration system and different ATP concentrations, we observed that NS3 establishes an ATP-dependent steady state between RNA unwinding and annealing, allowing modulation of the two opposing activities of this enzyme through ATP concentration. In addition, we observed that NS3 enhanced RNA-RNA interactions between molecules representing the ends of the viral genome that are known to be necessary for viral RNA synthesis. We propose that, according to the ATP availability, NS3 could function regulating the folding or unfolding of viral RNA structures.

Several dispositional traits have been examined in mating contexts by evolutionary psychologists. Such traits include life history strategy, sociosexuality, and the Big Five. Recently, scholars have examined the validity and predictive utility of mating intelligence, a new construct designed to capture the cognitive processes that underlie mating psychology. The current research employed a battery of dispositional traits that include all these constructs in an effort to predict preferences for different kinds of sex acts. Sexual acts vary wildly, and the ability to predict this variability may well hold an important key to underlying sexual strategies. A sample of 607 young adults (144 males and 463 females) completed measures of each of these traits as well as a measure of preference for specific sex acts (along with providing information on their sexual orientation). The traits predicted variability in preference for sex acts - with mating intelligence being the most predictive (for instance, mating intelligence was positively related to preference for vaginal intercourse across the sexes). Sex differences emerged (e.g., males show a stronger preference for anal sex than do females). Discussion focuses on (a) sex differences in preference for sex acts along with (b) why the trait variables predicted preferences in sex acts.

The ability to automatically and implicitly detect complex and noisy regularities in the environment is a fundamental aspect of human cognition. Despite considerable interest in implicit processes, few researchers have conceptualized implicit learning as an ability with meaningful individual differences. Instead, various researchers (e.g., Reber, 1993; Stanovich, 2009) have suggested that individual differences in implicit learning are minimal relative to individual differences in explicit learning. In the current study of English 16-17year old students, we investigated the association of individual differences in implicit learning with a variety of cognitive and personality variables. Consistent with prior research and theorizing, implicit learning, as measured by a probabilistic sequence learning task, was more weakly related to psychometric intelligence than was explicit associative learning, and was unrelated to working memory. Structural equation modeling revealed that implicit learning was independently related to two components of psychometric intelligence: verbal analogical reasoning and processing speed. Implicit learning was also independently related to academic performance on two foreign language exams (French, German). Further, implicit learning was significantly associated with aspects of self-reported personality, including intuition, Openness to Experience, and impulsivity. We discuss the implications of implicit learning as an ability for dual-process theories of cognition, intelligence, personality, skill learning, complex cognition, and language acquisition., (2010 Elsevier B.V. All rights reserved.)

Individuals with autism spectrum condition (ASC) have diagnostic impairments in skills that are associated with an implicit acquisition; however, it is not clear whether ASC individuals show specific implicit learning deficits. We compared ASC and typically developing (TD) individuals matched for IQ on five learning tasks: four implicit learning tasks--contextual cueing, serial reaction time, artificial grammar learning, and probabilistic classification learning tasks--that used procedures expressly designed to minimize the use of explicit strategies, and one comparison explicit learning task, paired associates learning. We found implicit learning to be intact in ASC. Beyond no evidence of differences, there was evidence of statistical equivalence between the groups on all the implicit learning tasks. This was not a consequence of compensation by explicit learning ability or IQ. Furthermore, there was no evidence to relate implicit learning to ASC symptomatology. We conclude that implicit mechanisms are preserved in ASC and propose that it is disruption by other atypical processes that impact negatively on the development of skills associated with an implicit acquisition.

Gamma carbonic anhydrases (gammaCA) are widespread in Prokaryotes. In Eukaryotes, homologous genes were found only in plant genomes. In Arabidopsis and maize, the corresponding gene products are subunits of mitochondrial Complex I. At present, only gammaCA homotrimers of Methanosarcina thermophila (CAM) show reversible carbon dioxide (CO(2)) hydration activity. In the present work, it is shown that recombinant plant gammaCA2 could form homotrimers and bind H(14)CO(3)(-). However, they are unable to catalyse the reversible hydration of CO(2). These results suggest that plant gammaCAs do not act as carbonic anhydrases but with a related activity possibly contributing to recycle CO(2) in the context of photorespiration.

Although 1-anilino-naphthalene-8-sulfonate (ANS) has been widely used in protein folding and binding studies, the detailed mechanism of this interaction is not fully understood. In this work the binding of ANS was analyzed at pre-equilibrium and equilibrium conditions using bovine serum albumin (BSA) as model. We employed a combined approach including the analysis of fluorescence, near-UV circular dichroism and isothermal titration calorimetric data. Experiments at equilibrium with these techniques identify three ANS molecules bound at hydrophobic cavities in BSA. Pre-equilibrium fluorescence analysis unambiguously indicated that the binding of ANS at hydrophobic cavities of BSA occurs at two different and independent classes of sites with similar affinities and quantum yields, two features that are undetectable by the equilibrium analysis. The binding of ANS to the first site is thermodynamically favored by similar contributions of the enthalpic (DeltaH = -22 kJ/mol) and entropic terms (-TDeltaS = -17 kJ/mol), while the binding to the second site is enthalpically driven (DeltaH = -31 kJ/mol; -TDeltaS = -0.6 kJ/mol). Complementary information from molecular docking showed three ANS molecules bound at hydrophobic cavities in BSA subdomains IIA and IIIA with binding affinities in the order of those found experimentally and three additional ANS molecules bound at water exposed sites.

This study examined how the quaternary organic ammonium ion, benzyltriethylamine (BTEA), binds to the Na,K-ATPase to produce membrane potential (V(M))-dependent inhibition and tested the prediction that such a V(M)-dependent inhibitor would display electrogenic binding kinetics. BTEA competitively inhibited K(+) activation of Na,K-ATPase activity and steady-state (86)Rb(+) occlusion. The initial rate of (86)Rb(+) occlusion was decreased by BTEA to a similar degree whether it was added to the enzyme prior to or simultaneously with Rb(+), a demonstration that BTEA inhibits the Na,K-ATPase without being occluded. Several BTEA structural analogues reversibly inhibited Na,K-pump current, but none blocked current in a V(M)-dependent manner except BTEA and its para-nitro derivative, pNBTEA. Under conditions that promoted electroneutral K(+)-K(+) exchange by the Na,K-ATPase, step changes in V(M) elicited pNBTEA-activated ouabain-sensitive transient currents that had similarities to those produced with the K(+) congener, Tl(+). pNBTEA- and Tl(+)-dependent transient currents both displayed saturation of charge moved at extreme negative and positive V(M), equivalence of charge moved during and after step changes in V(M), and similar apparent valence. The rate constant (k(tot)) for Tl(+)-dependent transient current asymptotically approached a minimum value at positive V(M). In contrast, k(tot) for pNBTEA-dependent transient current was a "U"-shaped function of V(M) with a minimum value near 0 mV. Homology models of the Na,K-ATPase alpha subunit suggested that quaternary amines can bind to two extracellularly accessible sites, one of them located at K(+) binding sites positioned between transmembrane helices 4, 5, and 6. Altogether, these data revealed important information about electrogenic ion binding reactions of the Na,K-ATPase that are not directly measurable during ion transport by this enzyme.

We report a measurement of the angular distributions of Drell-Yan dimuons produced using an 800 GeV/c proton beam on a hydrogen target. The polar and azimuthal angular distribution parameters have been extracted over the kinematic range 4.5

Insulin-degrading enzyme (IDE) is central to the turnover of insulin and degrades amyloid beta (Abeta) in the mammalian brain. Biochemical and genetic data support the notion that IDE may play a role in late onset Alzheimer disease (AD), and recent studies suggest an association between AD and diabetes mellitus type 2. Here we show that a natively folded recombinant IDE was capable of forming a stable complex with Abeta that resisted dissociation after treatment with strong denaturants. This interaction was also observed with rat brain IDE and detected in an SDS-soluble fraction from AD cortical tissue. Abeta sequence 17-27, known to be crucial in amyloid assembly, was sufficient to form a stable complex with IDE. Monomeric as opposed to aggregated Abeta was competent to associate irreversibly with IDE following a very slow kinetics (t(1/2) approximately 45 min). Partial denaturation of IDE as well as preincubation with a 10-fold molar excess of insulin prevented complex formation, suggesting that the irreversible interaction of Abeta takes place with at least part of the substrate binding site of the protease. Limited proteolysis showed that Abeta remained bound to a approximately 25-kDa N-terminal fragment of IDE in an SDS-resistant manner. Mass spectrometry after in gel digestion of the IDE .Abeta complex showed that peptides derived from the region that includes the catalytic site of IDE were recovered with Abeta. Taken together, these results are suggestive of an unprecedented mechanism of conformation-dependent substrate binding that may perturb Abeta clearance, insulin turnover, and promote AD pathogenesis.

Occlusion of K (+) in the Na (+)/K (+)-ATPase can be achieved under two conditions: during hydrolysis of ATP, in media with Na (+) and Mg (2+), after the K (+)-stimulated dephosphorylation of E2P (physiological route) or spontaneously, after binding of K (+) to the enzyme (direct route). We investigated the sidedness of spontaneous occlusion and deocclusion of Rb (+) in an unsided, purified preparation of Na (+)/K (+)-ATPase. Our studies were based on two propositions: (i) in the absence of ATP, deocclusion of K (+) and its congeners is a sequential process where two ions are released according to a single file mechanism, both in the absence and in the presence of Mg (2+) plus inorganic orthophosphate (Pi), and (ii) in the presence of Mg (2+) plus Pi, exchange of K (+) would take place through sites exposed to the extracellular surface of the membrane. The experiments included a double incubation sequence where one of the two Rb (+) ions was labeled as (86)Rb (+). We found that, when the enzyme is in the E2 conformation, the first Rb (+) that entered the enzyme in media without Mg (2+) and Pi was the last to leave after addition of Mg (2+) plus Pi, and vice-versa. This indicates that spontaneous exchange of Rb (+) between E2(Rb 2) and the medium takes place when the transport sites are exposed to the extracellular surface of the membrane. Our results open the question if occlusion and deocclusion via the direct route participates in any significant degree in the transport of K (+) during the ATPase activity.

We report a high statistics measurement of Upsilon production with an 800 GeV/c proton beam on hydrogen and deuterium targets. The dominance of the gluon-gluon fusion process for Upsilon production at this energy implies that the cross section ratio, sigma(p+d-->Upsilon)/2sigma(p+p-->Upsilon), is sensitive to the gluon content in the neutron relative to that in the proton. Over the kinematic region 0

We report a measurement of the angular distributions of Drell-Yan dimuons produced using an 800 GeV/c proton beam on a deuterium target. The muon angular distributions in the dilepton rest frame have been measured over the kinematic range 4.5